Combining hu14.18-IL2 and NK cell infusions to treat neuroblastoma
Combining hu14.18-IL2 and NK cell infusions to treat neuroblastoma
批准号:
10194408
负责人:
Christian Capitini
金额:
$34.71万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-07-03 至 2023-05-31
关键词:
Activated Natural Killer CellAllogenicAnimal ModelAntibodiesAntigen-Presenting CellsAntigensAutologousBiologicalCellsChemotherapy and/or radiationChildChildhoodChildhood LeukemiaClinicalClinical TrialsCombination immunotherapyDetectionDiseaseEffector CellEnvironmentFluorineGoalsGraft-Versus-Tumor InductionGranulocyte-Macrophage Colony-Stimulating FactorHematopoietic Stem Cell TransplantationHematopoietic stem cellsHigh Dose ChemotherapyIL2 geneImmuneImmune systemImmunologicsImmunomodulatorsImmunotherapyIn VitroIndividualInfusion proceduresInjectionsInterleukin-15Interleukin-2IsotopesLabelLeadLifeLigandsLinkLymphomaMagnetic Resonance ImagingMediatingMethodsModelingMonoclonal AntibodiesMusNational Cancer InstituteNatural Killer CellsNeuroblastomaOperative Surgical ProceduresPathway interactionsPatientsProductionRadiationRefractoryRelapseReportingResearchResearch PriorityResearch SupportResidual NeoplasmRoleRouteSTAT1 geneSensitivity and SpecificitySolid NeoplasmStem cell transplantSurfaceTNF geneTestingTimeToxic effectTransfusionTranslatingTranslationsTransplantationantitumor effectchemotherapyclinical applicationclinically translatabledetection platformdisorder riskgraft vs host diseasehigh riskhumanized monoclonal antibodiesimmunological synapseimmunoregulationimprovedin vivoinnovationkiller immunoglobulin-like receptornovelnovel strategiesnovel therapeuticspatient responsephase II trialpre-clinicalresearch clinical testingresponsesialogangliosidesstandard of caresuccesstraffickingtumor
中文摘要
神经母细胞瘤是儿童中最常见的颅外实体瘤,其表达的肿瘤类型为
英文摘要
Neuroblastoma is the most common extracranial solid tumor seen in children, and expresses the
disialoganglioside GD2 on its surface. For patients who have high risk disease or whose disease recurs after
completing therapy, there are limited options. Allogeneic hematopoietic stem cell transplant (AlloHSCT) is a
transfusion of hematopoietic stem cells from a healthy donor to a patient who has been treated with high doses
of chemotherapy and/or radiation, and is typically used clinically for children with leukemia or lymphoma. But
alloHSCT has had limited success thus far in attacking neuroblastoma with a graft-versus-tumor (GVT) effect,
and has introduced lethal graft-versus-host-disease (GVHD). The long term objective of this proposal is to
enhance the GVT effect against neuroblastoma. This proposal explores 3 specific aims to improve GVT effects
using animal models of alloHSCT. First we will explore usage of an immunocytokine called hu14.18-IL2, a
humanized GD2 monoclonal antibody linked to interleukin (IL)-2, to enhance the GVT effect, improving the
efficacy of the transplant. This antibody has already been given to children with neuroblastoma in clinical trials
but is not curative, and has not been tested in the alloHSCT setting. Second, we will activate allogeneic natural
killer (NK) cells with IL-15 and CD137L-expressing artificial antigen presenting cells, and infuse them for the
first time with hu14.18-IL2 as a combination strategy for improving GVT further. We will control any potential
GVHD by inhibiting the JAK/STAT pathway and blocking tumor necrosis factor-alpha production. Lastly, we will
label NK cells with a nonradioactive isotope of fluorine (¹⁹F) that will make these cells detectable by MRI,
determine how ¹⁹F-labeled NK cells traffic to neuroblastoma tumors after alloHSCT and if hu14.18-IL2 can
further attract NK cells to the tumor. The ultimate goal is to support the research priorities of the National
Cancer Institute by developing research that will lead to novel therapies for neuroblastoma. Success of any of
the individual aims will be a major advance in making alloHSCT more effective for neuroblastoma. Successful
translation of the entire proposal will lead to an innovative combination immunotherapy platform for treating
neuroblastoma.
期刊论文(0)
专著(0)
科研奖励(0)
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Combining hu14.18-IL2 and NK cell infusions to treat neuroblastoma
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依托单位:
海外基金